Oldenburg Kevin, Pooler Douglas, Scudder Kurt, Lipinski Christopher, Kelly Michele
MatriCal, Inc., Spokane, WA, USA.
Comb Chem High Throughput Screen. 2005 Sep;8(6):499-512. doi: 10.2174/1386207054867364.
Dissolution of organic compounds in DMSO in HTS plate or tube format is a difficult problem as users move to higher compression plate formats. Precipitation of compounds from DMSO screening stocks is a recognized problem in the HTS materials management process. The adverse effect of freeze thaw cycles on DMSO stock solutions stored in plate format as a result of cherry picking operations has led to the gradual replacement of plate-based storage with tube-based storage so as to minimize the number of freeze thaw cycles. Compound solubility in DMSO is markedly decreased by uptake of small quantities of water. We attribute this effect to the non ideal properties of DMSO water mixtures such that cavity formation in solvent, a necessary step in dissolution, is more difficult in wet DMSO than in dry DMSO or in pure water. We report here that efficient compound dissolution is possible even in 384 well format by the use of in-well plate-based sonication. Surprisingly, compounds precipitated from DMSO stocks either by water uptake or repeated freeze thaw cycles can be re-dissolved by low energy sonication. Finally, we demonstrate that precipitation of compound from DMSO stock solutions is synergistically enhanced by water uptake into DMSO compound stock solutions as well as by increasing the number of freeze thaw cycles.
随着用户转向更高压缩比的微孔板格式，在高通量筛选（HTS）微孔板或试管中溶解有机化合物成为一个难题。在HTS材料管理过程中，化合物从二甲基亚砜（DMSO）筛选储备液中沉淀是一个公认的问题。由于挑选操作导致以微孔板形式储存的DMSO储备液经历冻融循环，产生了不利影响，因此逐渐用基于试管的储存方式取代基于微孔板的储存方式，以尽量减少冻融循环的次数。少量水分的吸收会显著降低化合物在DMSO中的溶解度。我们将这种效应归因于DMSO - 水混合物的非理想性质，即溶剂中形成空穴（溶解过程中的一个必要步骤）在潮湿的DMSO中比在干燥的DMSO或纯水中更困难。我们在此报告，通过使用基于微孔板的孔内超声处理，即使在384孔板格式中也能实现化合物的有效溶解。令人惊讶的是，因水分吸收或反复冻融循环而从DMSO储备液中沉淀的化合物可以通过低能量超声处理重新溶解。最后，我们证明，DMSO化合物储备液中水分的吸收以及冻融循环次数的增加会协同增强化合物从DMSO储备液中的沉淀。
